[The influence of 6-months treatment with exenatide on type 2 diabetes mellitus compensation, anthropometric and biochemical parameters]. / Vliv 6mesícního podávání exenatidu na kompenzaci diabetes mellitus 2. typu, antropometrické a biochemické parametry.

OBJECTIVES: Exenatide, a synthetic GLP-1 analogue, is a new antidiabetic agent from the group ofincretine mimetics coming into the daily clinical practice. In our study we evaluated the effect of 6-months treatment with exenatide on diabetes compensation, anthropometric and biochemical parameters in the patients with poorly controlled type 2 diabetes mellitus and obesity. METHOD: We included 18 patients with poorly controlled diabetes (mean HbA1c 8.5 +/- 0.3%) treated with diet and peroral antidiabetic agents (4 patients were treated with insulin in the past). Exenatide was administered via subcutaneous injection twice daily for 6 months. Patients were examined after 1 month, when the dose ofexenatide was increased from 5 microg twice daily to 10 microg twice daily and after 3 and 6 months. We evaluated the diabetes compensation, biochemical parameters, body weight changes and side effects ofexenatide. RESULTS: 6-months exenatide treatment significant decreased body weight (baseline vs 6 month treatment 107.3 +/- 4.4 kg vs 103.7 +/- 4.6 kg, p = 0.02), BMI (36.7 +/- 1.2 kg/m2 vs 35.3 +/- 1.3 kg/m2, p = 0.01) a HbA1c (8.5 +/- 0.3% vs 7.4 +/- 0.4%, p = 0.04) and increased HDL-cholesterol (0.92 +/- 0.1 mmol/l vs 0.98 +/- 0.1 mmol/l, p = 0.02). Fasting glycemia tended to decline at the end of the study, but the difference did not reach the statistical significance. The area under the curve of glycemia levels after the standardized breakfast in the subgroup of 8 patients after the 6-months exenatide treatment was significantly lower when compared to baseline values (2,908 +/- 148 vs 2,093 +/- 194, p = 0.03). Concentrations of total and LDL-cholesterol and triglycerides did not change significantly. The most frequent side effects of exenatide treatments were transient anorexia and nausea (38.5%), dyspepsia and functional gastrointestinal discomfort (38.5%) and various neuropsychical symptoms (nervosity and insomnia - 30.8%). Most of the side effects disappeared during the treatment, none of these side effects was a reason for discontinuation of a treatment. 3 minor hypoglycemic episodes occured in patients simultaneously treated with derivates of sulfonylurea, but no serious hypoglycemia occured during the entire study. CONCLUSION: Exenatide treatment in obese patients with poor diabetes control was accompanied by statistically significant decrease of body weight, improvement of diabetes control and increase in HDL-cholesterol.

Serum adipocyte fatty acid binding protein levels in patients with type 2 diabetes mellitus and obesity: the influence of fenofibrate treatment.

Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-alpha agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-alpha agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6+/-2.1 microg/l, T2DM before F: 55.6+/-5.7 microg/l, T2DM after F: 54.2+/-5.4 microg/l, p 0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCR(glc)/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus.

Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype.

Genes for adiponectin and resistin are candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms (SNP) 45T>G and 276G>T of the adiponectin gene and 62G>A and -180C>G of the resistin gene in patients with obesity (OB), anorexia nervosa (AN) and in control healthy normal-weight women (NW) and to study the influence of particular genotypes on serum concentrations of these hormones and on insulin sensitivity. Serum adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), insulin, cholesterol, glycated hemoglobin (HbA1c) and blood glucose levels were measured in 77 patients with OB, 28 with AN and 38 NW. DNA analysis was carried out by polymerase chain reaction with restriction analysis of PCR product. The presence of SNP ADP+276 G>T allele was accompanied by higher cholesterol levels in AN patients, higher adiponectin concentrations in OB patients and lower HbA1c levels in NW. SNP of the resistin gene 62G>A was associated with lower HbA1c in NW and higher cholesterol concentrations in OB group. The carriers of the minor G allele in the position -180 of the resistin gene within AN group had significantly higher BMI relative to non-carriers. We conclude that polymorphisms in adiponectin and resistin genes can contribute to metabolic phenotype of patients with obesity and anorexia nervosa.

Comparisin of low energy breakfast based on special egg white spread product with a standard breakfast.

AIM: The aim of the study was to evaluate the influence of a new form of low calorie breakfast in comparison to standard low fat cheese breakfast. A special spread based on egg white was used (Energy content per 100 g: 319 kJ versus 802 kJ, fat content 1.15 g versus 15 g). Egg white derived products are widely used for weight reduction in Czech Republic. METHODS: 12 non-diabetic patients were included into the study (7 men and 5 women), mean age 38.5+/-10.7 years, and mean BMI 24.6 kg/m2. Standard breakfast was served first in a time interval of 1 week (Krajanka cheese) and after a week wash-out period low energy breakfast based on egg white was served for the same time. Glucose level, insulinaemia and C peptide were evaluated in 0, 60, 120 minute after breakfast. Psychological questionnaire was used to evaluate the taste and satiety. RESULTS: Standard breakfast: insulinaemia 6.3...34.6...11.0 IU, C peptide 0.6...1.6...1.0 pmol/l, glucose 5.0...5.4...4.8 mmol/I Low energy breakfast: insulinaemia 6.6...24.6...10.7 IU, C peptide 0.6...1.4...1.0 pmol/I, glucose 4.8...5.1...5.0 mmol/l. Paired t-test was used for evaluation. No difference in blood glucose level was found, borderline significances of insulinaemia in 60 minute (p= 0.056) and in C peptide (p= 0.089). Significant difference in decrease of insulinaemia between 60 and 120 minute (p=0.03) and borderline significant decrease in C peptide (p=0.055) shows shorter insulin secretion after low calorie breakfast and good insulin sensitivity in this group of lean subjects. Higher satiety and less-worthier taste were found using low energy breakfast. CONCLUSION: Low calorie breakfast induces lower and shorter insulin secretion and has a good metabolic effect in lean subjects. Testing in obese subjects will follow. Egg white derived low calorie products have a beneficial effect on insulin response without any difference in ingested carbohydrate quantity.

[The influence of very-low-calorie diet on soluble adhesion molecules and their gene expression in adipose tissue of obese women]. / Vliv nízkokalorické diety na sérové koncentrace a expresi cytoadhezivních molekul v tukové tkáni u obézních zen.

BACKGROUND: Adhesion molecules (AM) are proteins expressed on the endothelial surface that play an important role in development of endothelial dysfunction. Higher concentrations of AM were found in patients with atherosclerosis, obesity or type 2 diabetes mellitus. The aim of our study was to measure serum concentrations and gene expression of ICAM-1 (intercellular adhesion molecule 1), VCAM-1 (vascular adhesion molecule 1) and E-selectin in subcutaneous adipose tissue samples obtained by needle biopsy from obese women and healthy controls and to evaluate the effect of 3-weeks very-low-calorie diet (VLCD) on these parameters. METHODS AND RESULTS: 20 obese women (BMI 46.2 +/- 9.7 kg/m2) and 13 lean control women (BMI 23.8 +/- 2.3 kg/m2) were included into the study. Gene expression of AM in subcutaneous adipose tissue was measured using RT-PCR, serum AM levels were measured by multiplex immunoanalysis. At the baseline, serum E-selectin concentrations were higher in obese women compared to controls (24.4 +/- 2.3 vs. 15 +/- 1,5 ng/ml, p < 0,05). 3 weeks of VLCD significantly decreased BMI and serum E-selectin levels. Baseline mRNA expression of E-selectin, ICAM-1 and VCAM-1 in subcutaneous adipose tissue was lower in obese relative to lean women (p < 0.05). Weight reduction increased ICAM-1 and VCAM-1 gene expression (p < 0.05). CONCLUSIONS: Our results suggest that the subcutaneous adipose tissue is not the major source of the studied soluble adhesion molecules in obese women and that the regulation of AM local gene expression in subcutaneous adipose tissue probably differs from its circulating levels.

Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes.

PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.

[Laparoscopic gastric tubulization--sleeve gastrectomy--another option for bariatric food intake restriction in morbidly obese subjects]. / Laparoskopická tubulizace zaludku--sleeve gastrectomy--dalsí moznost bariatrické restrikce príjmu stravy u morbidne obézních jedincu.

INTRODUCTION: Nowadays, obesity is the commonest multifactorial metabolic disorder. The role of bariatric surgery, i.e. surgery specializing in the treatment of obesity, in the management of obese patients, where conservative therapy failed and who have high incidence of obesity relapses, or in morbidly obese subjects (BMI > 40, resp. BMI > 35), as well as in superobese subjects (BMI > 60), is irreplacable. Most of the surgical procedures for the morbid obesity treatement use miinvasive laparocopic techniques. Recent options include the method of gastric tubulization- Sleeve Gastrectomy (SG), which , as a "single procedure" has been performed in some clinics since 2003. MATERIAL AND METHODOLOGY: In the 1st Surgical Clinic of the 1st Medical faculty of the Charles University and General Faculty Hospital, the authors have intensively studied the problematics of bariatric surgery since 1983. Since Janury 2006, a total of 39 morbidly obese patients (MO), where adjustable gastric bandage had not been indicated for various reasons, have been indicated for laparoscopic sleeve gastrectomy. Gastric bandage was not indicated, for instance, in cases where poor cooperation ("sweet-eaters, binge-eaters") could be expected or when good cooperation and adherence to diet restrictions in patients with SAGB could not be guaranteed. RESULTS: Our study group of 39 morbidly obese patients included 30 females and 9 males. The mean age was 37.6 y.o.a., the mean weight was 127 kg, the mean height 164 cm and the mean BMI was 41.3. A nine- month follow up phase could be assessed only in 27 heavily obese subjects following SGs. The mean weight loss was 17.3 kg, the mean percentile excess weight loss (EWL) was 28.1% and the final mean reduction in BMI was 12.1. No serious late complications were recorded in the study group. CONCLUSION: Sleeve gastrectomy presents with a rather higher risk rates compared to gastric bandage, however, the risk remains considerably lower compared to that in malabsorption procedures. Unfortunately, there is no long- term experience regarding maintanance of the weight loss or possible development of serious late complications. Current excellent long- term weight reduction clinical results are very promissing.

Adipocytokines and cancer.

Adipose tissue-produced hormones significantly affect the metabolism of lipids and carbohydrates as well as numerous other processes in human body. It is generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and insulin resistance/diabetes. Epidemiological studies underlined that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Multiple recent studies have indicated that some of adipose tissue-derived hormones may significantly influence the growth and proliferation of tumorous stroma and malignant cells within. Here we review current knowledge about possible relationship of leptin and adiponectin to the etiopathogenesis of different malignant tumors. Most of the studies indicated that while leptin may potentiate the growth of cancer cells in vitro, adiponectin appears to have an opposite effect. Further studies are necessary to decide whether obesity-induced endocrine dysfunction of adipose tissue can directly influence carcinogenesis in different tissues and organs.

The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women.

The aim of our study was to determine whether adipocyte-derived hormones leptin, adiponectin and resistin contribute to the improvement of insulin sensitivity after very-low calorie diet (VLCD). Therefore, serum levels of these hormones were measured in fourteen obese females before and after three weeks VLCD and in seventeen age- and sex-matched healthy controls. Body mass index, HOMA index, serum insulin and leptin levels in obese women before VLCD were significantly higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA 10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml, leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and soluble leptin receptors levels were significantly lower in obese women before VLCD than in the control group. No differences were found in serum glucose and resistin levels between the obese group before VLCD and the control group. VLCD significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels and increased soluble leptin receptor levels. The changes in serum adiponectin and resistin levels in obese women after VLCD did not reach statistical significance. We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not. Therefore, other mechanisms rather than changes in the endocrine function of the adipose tissue are probably involved in the VLCD-induced improvement of insulin sensitivity.

[Polymorphisms of adiponectin and resistin genes in patients with obesity and anorexia nervosa]. / Polymorfismy genu pro adiponectin a rezistin u pacientek s mentální anorexií a obezitou--pilotní studie.

BACKGROUND: Adiponectin and resistin are hormones that may represent a link between obesity and insulin resistance. Genes for these hormones are new candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms 45T > G and 276T > G of adiponectin gene and 62G > A and -180C > G of resistin gene in patients with obesity, anorexia nervosa and in lean women and to study the influence of particular genotypes on serum concentrations of these hormones. METHODS AND RESULTS: Serum adiponectin, resistin, TNF-alfa and insulin levels were measured in 51 patients with obesity, 17 with anorexia nervosa and 17 lean women. DNA analysis was carried out by means of polymerase chain reaction (PCR) with restriction analysis of PCR product (RFLP). Adiponectin levels were lowest in obese women and highest in anorexia nervosa patients. Resistin concentrations were lowest in anorexia nervosa and highest in obese patients. Genotype analysis within respective groups showed no differences in assessed parameters when comparing different adiponectin and resistin polymorphisms. The only difference detected was significantly higher BMI in G/G genotype relative to T allele carries in 276 position of ADP gene in control group (23.48 +/- 0.85 vs. 19,7 +/- 0.95, p < 0.05). In anorexia nervosa patients, frequency of G allele in RETN -180 polymorphism was significantly higher relative to control group (p < 0.05). CONCLUSIONS: Polymorphisms 45T > G a 276T > G of ADP gene and 62G>A and -180C > G RETN gene did not influence serum ADP and RETN concentrations. BMI was influenced by T allele presence in 276 position of ADP gene in control group only. Anorexia nervosa patients had higher frequency of G allele of RETN -180 polymorphism compared to healthy women.

Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment.

Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.

[Serum concentrations of adiponectin in patients with restrictive and purgative subtype of mental anorexia]. / Se'rové koncentrace adiponectinu u pacientek s restriktivním a purgativním podtypem mentální anorexie.

BACKGROUND: The aim of our study was to compare serum concentrations of adiponectin, leptin and other selected parameters in female patients with restrictive subtype of anorexia nervosa (n=15), (RMA), binge/purge subtype of anorexia nervosa (n=11) (PMA) with age-matched healthy females, (C, n=14). METHODS AND RESULTS: RMA patients had the most severely decreased body mass index (BMI) and serum leptin levels of the three groups studied. These parameters were also significantly lower in PMA relative to C group. (BMI: RMA 14.61 +/- 0.49 kg/m2, PMA 17.30 +/- 0.25 kg/m2, C 23.21 +/- 0.96 kg/m2; leptin: RMA 1.39 +/- 0.31 ng/ml, PMA 3.72 +/- 0.77 ng/ml, C 9.17 +/- 1.53 ng/ml). In contrast, serum adiponectin levels were markedly increased in RMA patients (57.28 +/- 4.86 ug/ml) relative to other groups (PMA 40,25 +/- 2.18 microg/ml, K 26.84 +/- 2.40 microg/ml). Serum leptin levels positively correlated with BMI in all groups studied (r = 0.56, p = 0.002), while the inverse relationship was found for adiponectin levels and BMI (r = -0.72, p = 0.000003). The hormonal concentrations were measured by commercially available RIA and ELISA kits. CONCLUSIONS: The most significant changes of serum adiponectin and leptin levels were found in the RMA group with most severely decreased BMI and body fat content relative to rest of the groups. Possible role of increased adiponectin levels in the etiopathogenesis and/or metabolic changes in patients with anorexia nervosa is under the scope of our current investigations.